Impotence is a common disorder, which affects an estimated 10 million American men. In many people impotence has a profound effect on their well-being. Considerable advances have been made in the understanding of the physiology and pathophysiology of erectile function, however, many important questions remain unanswered. What is the role of the endothelium in penile erection? To what extent does the endothelium-dependent relaxation contribute to the initiation and maintenance of penile erection? How do alterations in endothelial function caused by disease states affect penile erectile function? Does the endothelium participate in the maintenance of smooth muscle resting tone and, therefore, in maintaining penile flaccidity? How do hypoxia and acidosis, which occur in veno-occlusive priapism, affect corporal smooth muscle contractility and perpetuate the priapistic erection? The general aim of this grant continues to be the study of the role of the corpus cavernosum vascular endothelium in the physiology and pathophysiology of penile erectile function. The present proposal will also focus on the pathophysiology of priapism and how the associated hypoxia and acidosis impair the normal reactivity of corporal smooth muscle and cause injury to the erectile tissue that can lead to erectile dysfunction. Human and rabbit corpus cavernosum tissue and cultured endothelial cells derived from these tissues will be used in these studies. The following specific aims are proposed: 1) To determine the balance between eicosanoids and nitric oxide in the modulation of corpus cavernosum smooth muscle tone. 2) To determine the effects of hypoxia and acidosis on the contractility of corpus cavernosum smooth muscle. 3) To determine the relationship between endothelium, membrane potential, ionic fluxes, and corpus cavernosum smooth muscle contractility. Alterations by hypoxia and acidosis. 4) To determine if an increase in adenosine production during hypoxia causes depression of corporal smooth muscle contractility.